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Preeclampsia: An Overview

  • lukemarshall93
  • 2 days ago
  • 9 min read

Introduction / Background

Preeclampsia is a serious pregnancy complication characterised by high blood pressure and signs of organ stress that develops after 20 weeks of pregnancy. Affecting 2-8% of pregnancies worldwide, it remains a leading cause of preventable maternal and infant deaths. The disease appears in two forms with different underlying causes: early-onset disease linked to placental problems, and late-onset disease connected to maternal health conditions. Both types involve an imbalance in blood vessel signalling proteins called sFlt-1 and PlGF.

When high-risk pregnancies are identified early, targeted prevention works well. Low-dose aspirin started before 16 weeks of pregnancy reduces severe preeclampsia by over 60%. However, current screening methods miss many cases and require expensive equipment unavailable in most developing countries, where nearly all preeclampsia deaths occur.


Key Facts:

  • Causes 76,000 maternal and 500,000 infant deaths annually

  • Early aspirin prevents over 60% of severe cases when started before 16 weeks

  • Women with previous preeclampsia face 2-8 times higher lifetime heart disease risk

  • Current screening detects 75-80% of severe cases but misses most mild cases

  • 99% of deaths occur in low-income countries lacking screening access


Disease Pathology

Preeclampsia develops through two different biological pathways that both damage blood vessel linings throughout the body. Early-onset disease occurs when placental cells fail to properly invade the uterine wall during early pregnancy, causing placental oxygen starvation that triggers release of anti-growth factors damaging maternal blood vessels. Late-onset disease happens when a woman's cardiovascular system cannot meet normal placental demands, often due to pre-existing conditions like obesity or chronic inflammation.

Both pathways increase sFlt-1, a protein that blocks growth signals needed for healthy blood vessels. This imbalance disrupts organs including kidneys, liver, brain, and blood clotting systems. The immune system also contributes through abnormal responses to the pregnancy and production of harmful autoantibodies against blood pressure receptors.


Pathophysiological Features:

  • Early-onset: defective placenta → oxygen starvation → blood vessel damage → severe complications

  • Late-onset: maternal health problems → inadequate circulation → milder but common disease

  • Immune dysfunction includes abnormal T-cell responses and autoantibodies

  • Genetic factors contribute, with heritability around 30-55%

  • sFlt-1/PlGF ratio test confirms or rules out diagnosis with over 90% accuracy


Prevalence

Preeclampsia affects 2-8% of pregnancies globally but varies widely by region. Developed countries report rates of 2-5% while developing countries see rates of 4-18%. Higher rates occur in populations with limited healthcare access, where late diagnosis increases mortality risk. In Australia, preeclampsia affects 5% of pregnancies overall but 8-12% of Indigenous pregnancies.

Several factors increase risk substantially, with first pregnancies carrying 3-4 times higher risk than later ones with the same partner. Women with chronic high blood pressure develop preeclampsia in 20-50% of pregnancies. Advanced maternal age, obesity, diabetes, kidney disease, and autoimmune disorders also elevate risk. Preeclampsia rates are rising in wealthy countries due to older mothers and increasing obesity.


Prevalence Patterns:

  • Early-onset (before 34 weeks): 10-15% of cases, highest infant mortality

  • Late-onset (34+ weeks): 85-90% of cases, greater maternal complications

  • Recurrence risk: 15-20% overall, up to 65% after severe early disease

  • Indigenous populations: 2-3 times higher rates in many countries

  • Chronic hypertension: 20-50% develop superimposed preeclampsia


Detection

First-trimester screening combines maternal health history with ultrasound and blood tests to identify high-risk pregnancies. The most effective approach integrates maternal factors, blood pressure measurement, uterine artery ultrasound, and PlGF blood test, detecting over 80% of severe cases. Using maternal factors alone detects only 40% of cases. Later in pregnancy, sFlt-1/PlGF ratio testing helps confirm or rule out suspected preeclampsia.

Major barriers limit screening access. Specialised ultrasound equipment costs $50,000-150,000 and requires trained operators, while PlGF tests need refrigerated transport and laboratory equipment. These requirements make screening impractical in resource-limited settings. Researchers are investigating newer approaches including cell-free DNA, metabolic markers, and antibody testing, though none are clinically validated yet.


Detection Methods:

  • Combined first-trimester screening: detects over 80% of severe cases but requires specialised ultrasound

  • Maternal factors alone: detects only 40% of cases

  • sFlt-1/PlGF ratio: confirms diagnosis with over 90% accuracy or rules it out with 99% certainty

  • Current screening costs $150-300 per test with specialised equipment

  • Infrastructure barriers limit access in developing countries where burden is highest


Treatment / Interventions

Delivery is the only cure for preeclampsia, with timing determined by balancing maternal safety with infant maturity. Prevention through aspirin offers the best results. Low-dose aspirin started before 16 weeks in high-risk women reduces severe preeclampsia by 62%, treating 50-72 women to prevent one case. Aspirin provides no benefit when started after 16 weeks, making early risk identification critical.

Managing active disease focuses on controlling blood pressure, preventing seizures, and choosing delivery timing. Blood pressure medications maintain safe levels without reducing placental blood flow. Magnesium sulfate reduces seizures by 58% and maternal death by 46% in severe disease. Corticosteroids given before early delivery reduce infant breathing problems by half. Blood pressure monitoring continues for at least two weeks after delivery, since nearly half of seizures occur postpartum.


Intervention Approaches:

  • Aspirin prophylaxis: prevents over 60% of severe cases but must start before 16 weeks

  • Blood pressure medications: labetalol, nifedipine, or methyldopa maintain safe levels

  • Magnesium sulfate: reduces seizures by 58% and death by 46% in severe disease

  • Calcium supplements: reduce disease by 55% in calcium-deficient populations

  • Screening and prevention become cost-effective within 5-10 years through reduced complications


Challenges

Current screening cannot accurately predict which individual pregnancies will develop preeclampsia during the critical first trimester when prevention works best. First-trimester screening detects 75-80% of severe early cases but only half of late-onset disease, which represents most cases. False positives occur in 10-15% of tests, causing unnecessary worry and interventions. Multiple biological pathways leading to similar symptoms complicate efforts to find universal biomarkers.

Infrastructure requirements create access barriers. Specialised ultrasound equipment and training are unavailable in most resource-limited areas. PlGF testing requires refrigeration, laboratory equipment, and two-day processing—impractical for remote regions. Treatment options beyond aspirin and delivery remain limited. Most women never receive recommended cardiovascular screening after preeclampsia despite doubled heart disease risk.


Key Challenges:

  • Prediction limitations: detects 75-80% of severe disease, only 50% of common late-onset cases

  • Infrastructure barriers: ultrasound and laboratory testing unavailable in most developing countries

  • LMIC access gap: 99% of deaths occur where screening infrastructure doesn't exist

  • Limited treatments: only aspirin works preventively, only before 16 weeks

  • Postpartum gaps: most women never receive recommended heart health monitoring


Opportunities

Systematic antibody testing across infectious and autoimmune causes remains unexplored despite known associations with preeclampsia. Helicobacter pylori CagA strains increase risk 2-3 times, while periodontal disease bacteria increase risk 2-4 times. Autoimmune conditions show the strongest links, with lupus increasing risk 9-fold and antiphospholipid syndrome 10-fold. Antibodies against blood pressure receptors correlate with severe disease. Testing multiple antibody types could identify different disease subtypes.

Antibody testing addresses infrastructure limitations. Antibodies remain stable in dried blood spots at room temperature for weeks, eliminating refrigeration needs. Standard ELISA technology uses equipment available in basic laboratories. Community health workers can collect dried blood spots, and successful infectious disease screening in developing countries demonstrates feasibility. Combining antibody profiles with clinical factors using computational approaches may improve prediction. Current aspirin use remains below 5% globally because screening is unavailable, so accessible testing could expand prevention.


Research Opportunities:

  • Comprehensive antibody screening across infections and autoimmune markers has not been done

  • Dried blood spots eliminate refrigeration and enable community-based collection

  • Standard laboratory equipment sufficient, unlike specialized ultrasound

  • Could distinguish infection-driven versus autoimmune disease types

  • May identify women at highest cardiovascular risk needing prevention


Links and References

Key Organizations


References

Global Burden and Epidemiology

  • Abalos E, Cuesta C, Grosso AL, Chou D, Say L. "Global and regional estimates of preeclampsia and eclampsia: a systematic review." Eur J Obstet Gynecol Reprod Biol 170:1-7 (2013)

  • Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. "Pre-eclampsia." The Lancet 376:631-644 (2010)

  • Say L, Chou D, Gemmill A, et al. "Global causes of maternal death: a WHO systematic analysis." Lancet Glob Health 2:e323-e333 (2014)

  • Ford ND, Cox S, Ko JY, et al. "Hypertensive Disorders in Pregnancy and Mortality at Delivery Hospitalization—United States, 2017–2019." MMWR 71:585-591 (2022)


Pathophysiology and Mechanisms

  • Levine RJ, Maynard SE, Qian C, et al. "Circulating angiogenic factors and the risk of preeclampsia." N Engl J Med 350:672-683 (2004)

  • Phipps EA, Thadhani R, Benzing T, Karumanchi SA. "Pre-eclampsia: pathogenesis, novel diagnostics and therapies." Nat Rev Nephrol 15:275-289 (2019)

  • Staff AC, Benton SJ, von Dadelszen P, et al. "Redefining preeclampsia using placenta-derived biomarkers." Hypertension 61:932-942 (2013)

  • Redman CW, Sargent IL. "Immunology of pre-eclampsia." Am J Reprod Immunol 63:534-543 (2010)

  • LaMarca B, Cornelius DC, Wallace K. "Elucidating immune mechanisms causing hypertension during pregnancy." Physiology (Bethesda) 28:225-233 (2013)


Prediction and Screening

  • Poon LC, Wright D, Rolnik DL, Syngelaki A, Delgado JL, et al. "Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women." Am J Obstet Gynecol 217:585.e1-585.e5 (2017)

  • O'Gorman N, Wright D, Syngelaki A, et al. "Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11–13 weeks gestation." Am J Obstet Gynecol 214:103.e1-103.e12 (2016)

  • Zeisler H, Llurba E, Chantraine F, et al. "Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia." N Engl J Med 374:13-22 (2016)

  • Rolnik DL, Wright D, Poon LC, et al. "Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia." N Engl J Med 377:613-622 (2017)


Prevention and Treatment

  • Henderson JT, Vesco KK, Senger CA, Thomas RG, Redmond N. "Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: Updated Evidence Report and Systematic Review for the USPSTF." JAMA 326:1192-1206 (2021)

  • Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. "Magnesium sulphate and other anticonvulsants for women with pre-eclampsia." Cochrane Database Syst Rev CD000025 (updated 2022)

  • Hofmeyr GJ, Lawrie TA, Atallah ÁN, Torloni MR. "Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems." Cochrane Database Syst Rev CD001059 (2018)

  • Dubon Garcia A, Devlieger R, Redekop WK, et al. "Cost-utility of a first-trimester screening strategy versus the standard of care for nulliparous women to prevent pre-term pre-eclampsia in Belgium." Pregnancy Hypertension 25:219-224 (2021)

  • Brown MA, Magee LA, Kenny LC, et al. "Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice." Hypertension 72:24-43 (2018)


Long-term Cardiovascular Risk

  • Bellamy L, Casas JP, Hingorani AD, Williams DJ. "Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis." BMJ 335:974 (2007)

  • Wu P, Haththotuwa R, Kwok CS, et al. "Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis." Circ Cardiovasc Qual Outcomes 10:e003497 (2017)

  • Garovic VD, White WM, Vaughan L, et al. "Incidence and Long-Term Outcomes of Hypertensive Disorders of Pregnancy." J Am Coll Cardiol 75:2323-2334 (2020)


Immune Mechanisms and Infections

  • Conde-Agudelo A, Villar J, Lindheimer M. "Maternal infection and risk of preeclampsia: systematic review and metaanalysis." Am J Obstet Gynecol 198:7-22 (2008)

  • Nieves C, Victoria da Costa Ghignatti P, Aji N, Bertagnolli M. "Immune Cells and Infectious Diseases in Preeclampsia Susceptibility." Can J Cardiol 40:2340-2358 (2024)

  • Siddiqui AH, Irani RA, Blackwell SC, et al. "Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severity." Hypertension 55:386-393 (2010)

  • Spinillo A, Beneventi F, Locatelli E, et al. "The impact of unrecognized autoimmune rheumatic diseases on the incidence of preeclampsia and fetal growth restriction: a longitudinal cohort study." BMC Pregnancy Childbirth 16:313 (2016)


Economic Burden

  • Stevens W, Shih T, Incerti D, et al. "Short-term costs of preeclampsia to the United States health care system." Am J Obstet Gynecol 217:237-248.e16 (2017)

  • Xu H, Shatenstein S, Ekambaram K, et al. "The health and economic burden of preeclampsia in the United States." Am J Obstet Gynecol MFM 4:100510 (2022)

  • Werner EF, Hauspurg AK, Rouse DJ. "A Cost-Benefit Analysis of Low-Dose Aspirin Prophylaxis for the Prevention of Preeclampsia in the United States." Obstet Gynecol 125:1375-1380 (2015)


Clinical Guidelines

  • Brown MA, Roberts L, Davis G, et al. "Hypertension in pregnancy: Guideline 2023." Society of Obstetric Medicine of Australia and New Zealand (2023)

  • American College of Obstetricians and Gynecologists. "Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222." Obstet Gynecol 135:e237-e260 (2020)

  • National Institute for Health and Care Excellence (NICE). "Hypertension in pregnancy: diagnosis and management (NG133)." (2019)


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